Method for preparing indenoisoquinoline derivatives

Abstract

A method for preparing indenoisoquinoline derivatives represented by the following formula (I) is disclosed, which comprises the following steps: (A) providing a first reactant represented by the following formula (II) and a second reactant represented by the following formula (III): and (B) reacting the first reactant represented by the formula (II) and the second reactant represented by the formula (III) in a solvent and selectively adding R 2 NH 2 therein, to obtain the indenoisoquinoline derivatives represented by the formula (I), wherein, R 1 , R 2 , R 3 , A, X, Y, Z, m and n are defined in the specification.

What is claimed is: 
     
       1. A method for preparing indenoisoquinoline derivatives represented by one of the following formulas (1) to (31), (34) to (39) and (41) to (46), comprising the following steps: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         (A) providing a first reactant represented by the following formula (II) and a second reactant represented by the following formula (III): 
       
       
         
           
           
               
               
           
         
         wherein A is —OH or —NHR 2 ; 
         X is —CO; 
         Y ring is a phenyl ring; 
         Z is F, Cl, Br or I; 
         n is an integral of 1 to 4; 
         each R 1  independently is H, nitro, Br, Cl or methoxy; or when n is 2, two adjacent R 1  and carbon atoms attached thereto together form a dioxolane; and 
         R 2  is H, methyl, ethyl, propyl, pentyl, allyl, phenyl, benzyl, morpholinoethyl, morpholinopropyl, imidazolpropyl, methoxyethyl, methoxypropyl, phenylbutyl, 4-fluorophenyl, 4-chlorophenyl, 
       
       
         
           
           
               
               
           
         
       
       wherein * is a bonding position, 
       
         
           
           
               
               
           
         
         wherein m is an integral of 1 to 4; and 
         each R 3  independently is H, Br, nitro or methoxy; or when m is 2, two adjacent R 3  and carbon atoms attached thereto together form a dioxolane; and 
         (B) reacting the first reactant represented by the formula (II) and the second reactant represented by the formula (III) in a solvent with a catalyst and adding R 2 NH 2  therein in the case where A is —OH, to obtain the indenoisoquinoline derivatives represented by one of the formulas (1) to (31), (34) to (39) and (41) to (46), wherein the catalyst comprises Cu +  or Cu 2+ . 
       
     
     
       2. The method of  claim 1 , wherein the solvent is water, MeCN, DMF, DMSO, dioxane, toluene, or a combination thereof. 
     
     
       3. The method of  claim 1 , wherein the catalyst is selected from the group consisting of CuI, CuSO 4 , CuCl, CuCl 2 , and a hydrate thereof. 
     
     
       4. The method of  claim 1 , wherein an alkali is further added in the step (B). 
     
     
       5. The method of  claim 4 , wherein the alkali is selected from the group consisting of K 2 CO 3 , Na 2 CO 3 , Cs 2 CO 3 , LiOH, NaOH, KOH, CsOH, Li 3 PO 4 , Na 3 PO 4 , K 3 PO 4  and Cs 3 PO 4 . 
     
     
       6. The method of  claim 1 , wherein Z in the formula (II) is I. 
     
     
       7. The method of  claim 1 , wherein the formula (II) is one of the following formulas (II-4) to (II-6): 
       
         
           
           
               
               
           
         
       
     
     
       8. The method of  claim 1 , wherein the formula (III) is one of the following formulas (III-1) to (III-4): 
       
         
           
           
               
               
           
         
       
     
     
       9. The method of  claim 1 , wherein the step (B) comprises the following steps in the case where A is —OH:
 (B1) reacting the first reactant represented by the formula (II) and the second reactant represented by the formula (III) in the solvent with the catalyst to obtain an intermediate represented by the following formula (IV), wherein the catalyst comprises Cu +  or Cu 2+ : 
 
       
         
           
           
               
               
           
         
         (B2) reacting the intermediate represented by the formula (IV) with R 2 NH 2  to obtain the indenoisoquinoline derivatives represented by one of the formulas (1) to (31), (34) to (39) and (41) to (46). 
       
     
     
       10. The method of  claim 9 , wherein the catalyst is selected from the group consisting of CuI, CuSO 4 , CuCl, CuCl 2 , and a hydrate thereof. 
     
     
       11. The method of  claim 9 , wherein an alkali is further added in the step (B1). 
     
     
       12. The method of  claim 11 , wherein the alkali is selected from the group consisting of K 2 CO 3 , Na 2 CO 3 , Cs 2 CO 3 , LiOH, NaOH, KOH, CsOH, Li 3 PO 4 , Na 3 PO 4 , K 3 PO 4  and Cs 3 PO 4 . 
     
     
       13. The method of  claim 9 , wherein an acid is further added in the step (B2). 
     
     
       14. The method of  claim 13 , wherein the acid is camphorsulfonic acid.